Dopamine D2 Receptor Activation Blocks GluA2/ROS Positive Feedback Loop to Alienate Chronic-Migraine-Associated Pain Sensitization

作者全名：Zhang, Wei; Zhang, Xiaoyan; Lei, Ming; Zhang, Dunke; Qin, Guangcheng; Zhou, Jiying; Ji, Lichun; Chen, Lixue

作者地址：[Zhang, Wei; Lei, Ming; Zhang, Dunke; Qin, Guangcheng; Chen, Lixue] Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, Chongqing 400016, Peoples R China; [Zhang, Xiaoyan; Zhou, Jiying] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400042, Peoples R China; [Ji, Lichun] Thirteenth Peoples Hosp Chongqing, Dept Respirat, Chongqing 400053, Peoples R China

通信作者：Chen, LX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, Chongqing 400016, Peoples R China.; Ji, LC (通讯作者)，Thirteenth Peoples Hosp Chongqing, Dept Respirat, Chongqing 400053, Peoples R China.

来源：ANTIOXIDANTS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001254474400001

JCR分区：Q1

影响因子：6

年份：2024

卷号：13

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：pain sensitization; GluA2; dopamine D2 receptor; mitochondrial calcium overload; oxidative stress

摘要：Chronic migraine is a disabling disorder without effective therapeutic medicine. AMPA receptors have been proven to be essential to pathological pain and headaches, but the related regulatory mechanisms in chronic migraine have not yet been explored. In this study, we found that the level of surface GluA2 was reduced in chronic migraine rats. Tat-GluR23Y (a GluA2 endocytosis inhibitor) reduced calcium inward flow and weakened synaptic structures, thus alleviating migraine-like pain sensitization. In addition, the inhibition of GluA2 endocytosis reduced the calcium influx and alleviated mitochondrial calcium overload and ROS generation in primary neurons. Furthermore, our results showed that ROS can induce allodynia and GluA2 endocytosis in rats, thus promoting migraine-like pain sensitization. In our previous study, the dopamine D2 receptor was identified as a potential target in the treatment of chronic migraine, and here we found that dopamine D2 receptor activation suppressed chronic-migraine-related pain sensitization through blocking the GluA2/ROS positive feedback loop in vivo and in vitro. Additionally, ligustrazine, a core component of ligusticum chuanxiong, was shown to target the dopamine D2 receptor, thereby alleviating ROS production and abnormal nociception in CM rats. This study provides valuable insight into the treatment of chronic migraine.

基金机构：National Science Foundation of Chongqing, China [CSTB2023NSCQ-MSX0172]; Graduate Teaching Innovation Team Project of the First Affiliated Hospital of Chongqing Medical University [CYYY-YJSJXCX-202310]

基金资助正文：This work was supported by the National Science Foundation of Chongqing, China (No:CSTB2023NSCQ-MSX0172), and the Graduate Teaching Innovation Team Project of the First Affiliated Hospital of Chongqing Medical University (CYYY-YJSJXCX-202310).